“Biochips” or arrays of binding agents, such as oligonucleotides and peptides, have become an increasingly important tool in the biotechnology industry and related fields. These binding agent arrays, in which a plurality of binding agents are present on a solid support surface in the form of an array or pattern, find use in a variety of applications, including gene expression analysis, drug screening, nucleic acid sequencing, mutation analysis, and the like.
Such arrays may be prepared in a number of different ways. For example, DNA arrays may be prepared manually by spotting DNA onto the surface of a substrate with a micro pipette. See Khrapko et al., DNA Sequence (1991) 1:375-388. Alternatively, the dot-blot approach, as well as the derivative slot-blot approach, may be employed in which a vacuum manifold transfers aqueous DNA samples from a plurality of wells to a substrate surface. In yet another method of producing arrays of biopolymeric molecules, a pin is dipped into a fluid sample of the biopolymeric compound and then contacted with the substrate surface. By using a plurality or array of pins, one can transfer a plurality of samples to the substrate surface at the same time. Alternatively, an array of capillaries can be used to produce biopolymeric arrays. See WO 95/35505. In another method of producing biopolymeric arrays, arrays of biopolymeric agents are “grown” on the surface of a substrate in discreet regions. See e.g. U.S. Pat. No. 5,143,854 and Fodor et al., Science (1991) 251:767-773.
Despite the variety of different methods available for the production of biopolymeric arrays, there are disadvantages associated with each method. For example, current methods of growing the polymeric agents on the surface of an array, such as the photoresist techniques described in Fodor supra, are expensive and require the use of specialized photosensitive protecting groups on the phosphoramidites. As such, there is continued interest in the development of new methods for producing polymeric arrays, particularly in the development of new methods for growing polymers on the surface of a substrate to produce an array.
Relevant Literature
Patents and patent applications describing arrays of biopolymeric compounds and methods for their fabrication and/or use include: U.S. Pat. Nos. 4,877,745; 5,143,854; 5,242,974; 5,338,688; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934;5,449,754; 5,472,672; 5,474,796; 5,510,270; 5,527,681; 5,529,756; 5,532,128; 5,545,531; 5,552,270; 5,554,501; 5,556,752; 5,658,802; 5,561,071; 5,599,695; 5,624,711; 5,639,603; 5,658,734; 5,670,322; 5,677,195; 5,698,089; 5,700,637; 5,723,320; 5,744,305; 5,759,779; 5,763,170; 5,846,708; WO 90/10716; WO 92/10588; WO 93/17126; WO 95/11995; WO 95/35505; WO 97/10365; WO 97/27317; WO 97/46313; EP 0 373 203 B1; EP 742 287 A2; and EP 799 897 A1.